Two men with arthritis walk into a room. Both have the same degree of damage to their knee cartilage, but only one rates his pain a nine on a scale of zero to 10. Why?

Roger Fillingim, Ph.D., is trying to find out with the help of a five-year, $5.5 million grant he recently received from the National Institutes of Health. Fillingim received the NIH’s Merit Award, which will allow him to further research on his current project – a study in understanding pain and limitations in osteoarthritic disease. Funds for the study, known as UPLOAD, will be shared with the University of Alabama at Birmingham, where data for the project also will be collected.

“The global goal of our research is to try to understand the multiple factors that conspire to produce higher levels of pain and disability in some people with knee osteoarthritis as opposed to other people with knee osteoarthritis,” Fillingim said.

Osteoarthritis, the most common form of arthritis, is characterized by destruction of the joints, reduction of the cartilage tissue and formation of bone spurs. The disease affects about 27 million Americans over the age of 25 but some experience its effects more profoundly than others. Similar stages of disease can cause extensive pain in one person and little-to-no discomfort in the next. One of Fillingim’s research goals is to understand why African-Americans with knee osteoarthritis tend to have higher levels of pain and disability than non-Hispanic whites.

“We recognize a health disparity; we want to correct a health disparity, but to correct it you have to understand the factors driving the disparity,” Fillingim said.

The study also seeks to understand how both psychological factors, such as environmental stress, and biological factors work together over time to drive neurobiological changes that alter the way the brain processes pain-related information. One factor the researchers intend to study is how inflammatory responses play into people’s varying pain reactions to the disease.

Researchers will measure participants’ blood for markers of systemic inflammation and markers of anti-inflammatory function, seeing if those who have higher levels of anti-inflammatory markers also report lower levels of pain. Fillingim hypothesizes that stress plays a major role in whether patients experience inflammation.

“We create the experience of pain; we don’t passively receive whether or not we’re having pain,” Fillingim said. “So, if your brain does something different with that incoming pain than my brain does, even though the incoming information is identical, you might feel the pain differently.”

The researchers will use brain-imaging technology to understand the way in which these brain processes influence how much pain or disability people have with arthritis. Participants’ responses are measured at baseline and then followed over a period of two years. While their symptoms may change – for better or for worse – researchers will be able to observe how participants’ brains react during the changes. Then they can begin to determine what is driving those changes.

“Is it life stress? Physical activity? There are a lot of factors that interact to influence what we ultimately find,” Fillingim said.

The NIH Merit Award is more than just a sum of money. To Fillingim, it is a crucial step in moving down the road to understanding why arthritic symptoms vary so much between people – and, eventually, to helping alleviate them.

“If you don’t understand the different factors that are contributing to pain, it’s hard to develop treatments that target the right things,” he said.